Detection Rate, Risk Factors, and Outcomes of Isolated Terminal Ileal Ulcers

Abstract

Aims/Background:

The detection rate of isolated terminal ileal ulcers (ITIU) is increasing during colonoscopy. However, its clinical significance remains unknown. This study aimed to explore the detection rate and risk factors of ITIU in individuals undergoing colonoscopy and evaluate the outcomes of patients with nonspecific ITIU.

Methods:

Overall, 11,504 consecutive individuals who underwent colonoscopy at Department of Gastroenterology, General Hospital of Northern Theater Command between 1 July 2021 and 31 December 2022 were retrospectively screened. Among the individuals who completed terminal ileum (TI) intubation, the detection rate of ITIU was calculated. Furthermore, among the individuals with complete baseline data, logistic regression analyses were performed to identify the independent factors associated with ITIU. At least one-year follow-up outcome after the index colonoscopy was evaluated in patients with nonspecific ITIU who received and did not receive empiric therapy.

Results:

Overall, 9649 individuals completed TI intubation with an ITIU detection rate of 1.3% (123/9649). Among them, 1709 individuals had complete baseline data and were further selected in the risk factor analysis. Compared with the non-ITIU group, the ITIU group was significantly younger (56 vs. 46, p = 0.010). Multivariate logistic regression analyses also demonstrated that age ≤50 years (adjusted odds ratio [aOR] = 1.947, 95% confidence interval [CI] = 1.056–3.587, p = 0.033) was independently associated with ITIU. There was no significant difference in clinical symptoms (p = 1.000) or colonoscopic findings (p = 0.560) between patients with nonspecific ITIU who received empiric therapy and observational follow-up.

Conclusion:

ITIU is not rare during colonoscopy. Young individuals may have a higher probability of suffering from ITIU. Empiric therapy may not be necessary for patients with nonspecific ITIU.

Graphical abstract

Keywords

ileal diseases / Crohn disease / age / body mass index / inflammatory bowel disease

1. Introduction

Terminal ileum (TI) refers to the intestinal tract from the ileocecal valve to the proximal end of the ileum, and its length is about 30–40 cm [1]. Feces tend to accumulate at the TI, more probably causing bacterial growth; meanwhile, there is a large amount of intestinal lymphoid tissue and Peyer’s patches within the TI [2, 3]. Therefore, it is more likely to develop ulcers in this region. Notably, if there was no ulcer at any other part of the intestines, isolated terminal ileal ulcers (ITIU) would be defined [1]. It has been reported that the detection rate of ITIU among individuals undergoing colonoscopy screening is 1.45% [4]. Among individuals with gastrointestinal symptoms, the detection rate of ITIU was observed to be 4.90% [5]. Until now, the etiology of ITIU has not been elucidated. It may be associated with infections, drugs, inflammatory bowel disease (IBD), eosinophilic gastroenteritis, ischemic bowel disease, and neoplasms [6, 7, 8, 9]. It has been reported that 1.07–34.5% of individuals with isolated terminal ileitis and ITIU may progress to Crohn disease (CD) during a long-term follow-up period, and the incidence of CD gradually increases over time [5, 8, 10, 11, 12]. Some investigators also suggest that nonspecific ITIU should be considered as an early stage of CD [5, 11, 12, 13], but it usually takes a relatively long time to progress from nonspecific ITIU to CD. Thus, early treatment and close monitoring may be required [5, 6, 8, 12]. However, there are no specific guidelines for the diagnosis and management of ITIU, because it is usually occult, asymptomatic, or nonspecific in symptoms.

Considering the clinical significance of ITIU, it is critical to understand the epidemiology of ITIU and recognize high-risk populations for developing ITIU. It has been reported that body mass index (BMI) may be associated with the number of small intestinal ulcers, but the association of BMI with ITIU was uncertain [14]. Additionally, other potential risk factors associated with ITIU have not been identified. The present study aimed to analyze the detection rate of ITIU and its associated risk factors to strengthen the knowledge of this disease and to explore the outcomes of nonspecific ITIU.

2. Methods

2.1 Study Design

We retrospectively screened the medical records of 11,504 consecutive individuals undergoing colonoscopy at the Department of Gastroenterology, General Hospital of Northern Theater Command, between 1 July 2021 and 31 December 2022. The inclusion criteria were the individuals who underwent colonoscopy at our department between 1 July 2021 and 31 December 2022. The exclusion criteria were as follows: (1) incomplete colonoscopy due to endoscopic therapy alone, endoscopic ultrasonography alone, or poor quality of bowel preparation, etc.; (2) history of ileocecal resection; (3) failed cecal intubation due to colonic stenosis from colorectal cancer or severe IBD, patients’ intolerable pain, or colonic redundancy; and (4) successful cecal intubation but without TI intubation. At the Department of Gastroenterology, TI intubation is routinely performed during colonoscopy. However, if the TI intubation is technically difficult or unsafe, endoscopists would not choose to attempt it. The study protocol was approved by the medical ethical committee of General Hospital of Northern Theater Command [Approval number: Y (2023)196]. All of our patients signed their informed consent forms for colonoscopy before undergoing the examination. As mentioned in the ethical approval document of our study protocol, considering the retrospective nature of this study, the use of anonymous data, the lack of direct intervention measures, and the extremely minimal risk to patients, the medical ethics committee of the General Hospital of the Northern Theater Command has waived the requirement for the patients’ written informed consents. This is in accordance with the principles outlined in the Declaration of Helsinki.

2.2 Data Collection

Data were collected if they were reported in the medical records [15], including demographics such as gender, age, and BMI; type of patient such as outpatient, inpatient; clinical symptoms such as abdominal pain, diarrhea gastrointestinal bleeding, abdominal distension/discomfort, constipation, formless stool, and screening/surveillance; endoscopic findings such as TI ulcer, ITIU, ileocecal valvulitis/colitis, colonic diverticulosis, and colonic polyp; and diagnoses such as CD, ulcerative colitis (UC), lymphoma, and ankylosing spondylitis. Histology of the ITIU was collected, and information regarding the management of nonspecific ITIU was also collected, mainly including empiric therapy and observational follow-up. Telephone follow-up at least one year after the index colonoscopy was performed in patients with nonspecific ITIU to collect clinical symptoms, colonoscopic findings during re-examination, and follow-up outcomes [1].

2.3 Definitions

ITIU was defined as ulcers occurring only in the terminal ileum during colonoscopy with TI intubation.

The detection rate of ITIU was defined as the percentage of individuals who were diagnosed with ITIU among the individuals with successful TI intubation.

The number of ulcers was defined as single and multiple. Single ulcer was defined as only one ulcerative lesion was found at the TI during colonoscopy. Multiple ulcers were defined as two or more ulcerative lesions were found at the TI during colonoscopy.

Individuals with a BMI of 18.5 kg/m² were defined as underweight, 18.5–23.9 kg/m² as normal-weight, 24.0–27.9 kg/m² as overweight, and \ge28 kg/m² as obese individuals [16].

2.4 Statistical Analyses

Normality was evaluated using the Kolmogorov-Smirnov test for continuous variables, and non-normal distribution data were presented as median [interquartile range (IQR)], and compared by the Mann-Whitney U test. Categorical variables were expressed as frequency (percentage), and compared by the Chi-square test, Chi-squared correction test, or Fisher’s exact test. Among the individuals with complete baseline data, demographics, BMI, and indications for colonoscopy were compared between ITIU and non-ITIU groups. Logistic regression analyses were performed to identify the independent factors associated with ITIU, and variables with p 0.10 in the univariate logistic regression analyses were further included in the multivariate logistic regression analyses. Collinearity was tested by using the variance inflation factor (VIF) and a VIF >2 was defined as problematic collinearity. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All statistical analyses were performed by using SPSS 26.0 (IBM Corp, Armonk, NY, USA), and a two-sided p 0.05 was considered statistically significant.

3. Results

3.1 Baseline Characteristics of Individuals

A total of 9649 individuals who completed TI intubation were included (Fig. 1). Their characteristics are described in Table 1. The median age was 53 years, 55.8% (5382/9648) of these individuals were older than 50 years, and 55.1% (5315/9649) were male. Among them, 143 individuals had TI ulcer, of whom 20 were also accompanied with ileocecal valve or colon ulcer. Therefore, the detection rate of ITIU was 1.3% (123/9649). Characteristics of patients with ITIU were described in Table 2. The median age was 44 years, 41.5% (51/123) of the patients with ITIU were older than 50 years, and 60.2% (74/123) were male. Among the patients with ITIU, 37.4% (46/123) were detected with a single ulcer. The proportion of patients who were accompanied with ileocecal valvulitis/colitis, colonic diverticula, and colonic polyp was 22.8% (28/123), 5.7% (7/123), and 44.7% (55/123), respectively. Among the 123 patients, 106 had the histology of the ulcers, of whom 99 (93.4%) indicated chronic inflammation and 63 (59.4%) lymphocyte proliferation.

A total of 1709 individuals had completed baseline data, and their characteristics were described in Table 3. The median age was 56 years, 51.3% (876/1709) were male, and 63.4% (1084/1709) were older than 50 years. The median BMI was 23.90 kg/m². Colonoscopy was performed for formless stool in 34.5%, for screening/surveillance in 31.6%, and for abdominal pain in 21.0%. The proportion of individuals with ITIU was 2.5% (43/1709).

3.2 Differences Between Non-ITIU and ITIU Groups

Compared with the non-ITIU group, the ITIU group was significantly younger (46 vs. 56, p = 0.010). In the ITIU group, the common indications for colonoscopy were formless stool (34.9%), screening/surveillance (32.6%), and abdominal pain (23.3%) (Table 4).

3.3 Factors Associated With ITIU

No significant multicollinearity was detected among the variables included in the multivariate logistic regression model (all VIF 2). Multivariate logistic regression analyses demonstrated that age \le50 years old (adjusted odds ratio [aOR] = 1.947, 95% CI = 1.056–3.587, p = 0.033) remained independently associated with ITIU (Table 5).

3.4 Diagnoses of ITIU

A total of 17 patients with ITIU had their specific causes, including 9 with drug-induced ulcer, 2 with CD, 3 with UC, 2 with lymphoma, and 1 with ankylosing spondylitis (Fig. 2).

3.5 Management and Outcomes of Nonspecific ITIU

A total of 106 patients who had nonspecific ITIU received empiric therapy, including 5-Aminosalicylic Acid (5-ASA), probiotics, and 5-ASA plus probiotics, and observational follow-up. Among them, 48 patients could not be further contacted during the follow-up period, and 58 could be followed by telephone at least one year after the index colonoscopy. Furthermore, 36 of the 58 patients received empiric therapy during their median follow-up period of 25 months, and another 22 did not receive further therapy during their median follow-up period of 23 months. Neither clinical symptoms (p = 1.000) nor colonoscopic findings (p = 0.560) were significantly different between patients who received empiric therapy and those who received observational follow-up assessment (Table 6).

4. Discussion

Our study showed that the detection rate of ITIU in individuals undergoing colonoscopy was 1.3% (123/9649). Among them, 4.1% (5/123) were diagnosed with IBD (2 with CD and 3 with UC). Common clinical manifestations of ITIU were formless stool and abdominal pain. In addition, age \le50 years was independently associated with ITIU. Subsequently, there was no difference in the follow-up outcomes between patients with nonspecific ITIU who received empiric therapy and those who received observational follow-up.

As well known, IBD often occurs in young adults, and the peak age of its onset is 18 to 49 years [17]. Considering a potential correlation between ITIU and IBD [5, 6], it is reasonable to believe that the age of individuals also influences the occurrence of ITIU, which is consistent with the findings of our current study. There are some possible explanations for this association, as follows. First, ITIU alone, without any involvement of the rest of the intestines, can be observed at the early stage of IBD [6, 18]. Specifically, nearly 30% of patients with CD have ulcers confined to the TI alone [19], and nearly 17% of patients with UC can be accompanied by ulcers in the TI [20]. Our study found that 10.7% (3/28) of patients with ITIU and concurrent ileocecal valvulitis/colitis were finally diagnosed with UC, probably because backwash ileitis resulted in ileal ulcers. Therefore, a higher risk of ITIU in individuals younger than 50 years old can be explained by a higher incidence of IBD in younger individuals [17]. Second, TI is a special part of the intestinal tract where feces tend to accumulate, and bacteria thrive. It contains a large amount of Peyer’s patches, which are responsible for the intestinal immune system or intestinal immunity. Notably, the number of Peyer’s patches gradually decreases with age, and peaks at the age of 15–25 years old. Once the bacteria thrive, the immune response would be strong at the TI owing to the presence of Peyer’s patches. Taken together, it is more likely to develop ulcers in the TI in young individuals [2, 3, 21, 22].

There seems to be a positive correlation between the number of small intestinal ulcers and BMI [14]. Previous studies suggest that the diversity of gut microbiota is lower in obese people [23, 24, 25]. Especially, most obese people have diets that are low in fiber but high in protein and fat. Notably, these diets can alter the ratios of microbes and metabolites that modulate inflammation [26, 27, 28]. Therefore, intestinal inflammation can be more easily increased in obese people. Moreover, the presence of certain bacteria in obese people can impair the function of intestinal tight junctions, allowing bacterial products to pass through the intestinal wall easily and then induce an inflammatory response [14, 23, 29]. By comparison, our study demonstrated only a marginally positive association between ITIU and BMI \ge28.0 kg/m². This issue can be further explored in large-scale studies.

At present, there is no consensus on routine TI intubation during screening colonoscopy. Traditionally, considering the time-consuming nature of TI intubation and a low detection rate of TI lesions, routine TI intubation is not recommended, and TI intubation is only recommended for individuals with gastrointestinal symptoms or suspected IBD [4, 30, 31]. However, our study showed that the detection rate of ITIU was 1.3% and that approximately 90% of individuals undergoing colonoscopy completed the TI intubation. Interestingly, we found that a relatively high proportion of ITIU individuals underwent screening colonoscopy, who did not have any obvious gastrointestinal symptoms and were asymptomatic. Thus, it seems that clinical manifestations are not associated with ITIU, and the necessity of TI intubation should be recognized in all individuals undergoing screening colonoscopy.

In a randomized controlled trial (RCT) enrolling 82 patients with ITIU, there was no significant difference in clinical efficacy or endoscopic outcome during short-term and 1-year follow-up periods between patients who received experimental treatment with mesalazine (orally, 4.0 g, quaque die [qd]) for 3 months and those who received observational follow-up [32]. Our current study also showed no significant difference in the efficacy between patients receiving empiric therapy and observational follow-up after 1-year follow-up. Recently, another RCT enrolling 60 patients with isolated terminal ileum abnormalities demonstrated no significant difference in clinical or endoscopic efficacy between patients who received combination antimicrobial therapy (rifaximin, orally, 550 mg, bid, for two weeks; albendazole, orally, 400 mg, as a single dose; tinidazole, orally, 1 g, bis in die [bid], for three days) and those who received symptomatic treatment (probiotics; proton pump inhibitors; prokinetic) during short-term and 3-month follow-up periods [33]. It has been reported that the rate of progression from ITIU to IBD is high, ranging from 29% to 54%, during a follow-up period of 4 to 7 years. Therefore, nonspecific ITIU should be considered as an early stage of IBD and treated early and monitored closely [13, 18, 34, 35, 36]. Considering that it is difficult to distinguish between IBD and ITIU, especially in asymptomatic individuals [10, 31], long-term follow-up and an adaptable treatment strategy seem to be necessary for patients with ITIU.

Our study has a few limitations. First, owing to the retrospective nature of this study, some baseline data, such as height, weight, and indications for colonoscopy, and follow-up information, were unavailable for all individuals. Second, in our study, some patients received probiotics or 5-ASA as empiric therapy for ileal ulcers. However, a systematic review and meta-analysis regarding the efficacy of aminosalicylic acid preparations for the treatment of CD revealed that the effectiveness of sulfasalazine for treating mild-to-moderate active CD was marginal. Additionally, olsalazine and mesalazine, at a low (1–2 g/d) or high (3.2–4.0 g/d) dosage, did not significantly differ from placebo in inducing remission of CD [37]. Furthermore, the current European Crohn’s and Colitis Organization guidelines do not recommend the use of oral 5-ASA for the treatment of ileal CD [38]. Finally, in our study, the BMI classifications are based on the China-specific criteria, which differ from the World Health Organization standards, particularly in establishing thresholds for overweight and obesity. This is primarily because the risk stratification of comorbidities and mortality in the Chinese population is dependent upon lower BMI cut-off values [39, 40, 41]. Further studies should validate this conclusion in population outside the China according to the World Health Organization standards of BMI.

5. Conclusion

In conclusion, ITIU is not rare during colonoscopy, and predominates in younger individuals with an age \le50 years. However, empiric therapy does not improve the outcomes of patients with nonspecific ITIU. Therefore, the cost-effectiveness or time-efficiency of TI intubation should be comprehensively evaluated in long-term follow-up studies.

Key Points

• ITIU had a detection rate of 1.3% and is predominantly observed in younger individuals with an age \le50 years.

• The necessity of TI intubation should be recognized in all individuals undergoing screening colonoscopy.

• Younger age is an independent risk factor for ITIU.

• Empiric therapy does not improve the outcomes of patients with nonspecific ITIU.

Availability of Data and Materials

All data included in this study are available from the corresponding authors upon reasonable request.

References

[1] He X, Chen Y, Zhou X, Lu C. Clinical Course and Prognosis of Isolated Terminal Ileal Ulcers. Archives of Iranian Medicine. 2023; 26: 434–438. https://doi.org/10.34172/aim.2023.66.

[2] Mörbe UM, Jørgensen PB, Fenton TM, von Burg N, Riis LB, Spencer J, et al. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal Immunology. 2021; 14: 793–802. https://doi.org/10.1038/s41385-021-00389-4.

[3] Abo-Shaban T, Sharna SS, Hosie S, Lee CYQ, Balasuriya GK, McKeown SJ, et al. Issues for patchy tissues: defining roles for gut-associated lymphoid tissue in neurodevelopment and disease. Journal of Neural Transmission. 2023; 130: 269–280. https://doi.org/10.1007/s00702-022-02561-x.

[4] Meral M, Bengi G, Kayahan H, Akarsu M, Soytürk M, Topalak Ö et al. Is ileocecal valve intubation essential for routine colonoscopic examination? European Journal of Gastroenterology & Hepatology. 2018; 30: 432–437. https://doi.org/10.1097/MEG.0000000000001065.

[5] Mehta V, Gupta A, Mahajan R, Narang V, Midha V, Sood N, et al. Symptomatic isolated terminal ileal ulcers: etiology and clinical significance. Endoscopy International Open. 2017; 5: E539–E546. https://doi.org/10.1055/s-0043-100688.

[6] Tseveldorj N, Gündüz C, Saraçoğlu YO, Dağlı Ü. Clinical Characteristics and Etiology of Terminal Ileum Ulcers: A Retrospective Study. The Turkish Journal of Gastroenterology. 2024; 35: 609–617. https://doi.org/10.5152/tjg.2024.23589.

[7] Sethi S, Puri R, Jain HP, Ashwin DK. A Rare Cause of Terminal Ileal Ulcer: Beyond Tuberculosis and Crohn’s Disease. Digestive Diseases and Sciences. 2025; 70: 2565–2567. https://doi.org/10.1007/s10620-025-09023-w.

[8] Kim WJ, Lee CM, Jang JO, Kim SJ, Choi CW, Park SB. Clinical features and differential diagnosis in symptomatic localized terminal ileitis or ulcer. Medicine. 2025; 104: e42432. https://doi.org/10.1097/MD.0000000000042432.

[9] Nguyen J, Lee S, Yang GY. Comprehensive Evaluation and Unique Morphologic Features of Nonsteroidal Anti-Inflammatory Drug (NSAID) Enteropathy in the Terminal Ileum. International Journal of Surgical Pathology. 2022; 30: 616–622. https://doi.org/10.1177/10668969221076549.

[10] Chang HS, Lee D, Kim JC, Song HK, Lee HJ, Chung EJ, et al. Isolated terminal ileal ulcerations in asymptomatic individuals: natural course and clinical significance. Gastrointestinal Endoscopy. 2010; 72: 1226–1232. https://doi.org/10.1016/j.gie.2010.08.029.

[11] O’Donnell S, Crotty PL, O’Sullivan M, Breslin N, O’Connor HJ, O’Morain CA, et al. Isolated active ileitis: is it a mild subtype of Crohn’s disease? Inflammatory Bowel Diseases. 2013; 19: 1815–1822. https://doi.org/10.1097/MIB.0b013e31828dc68b.

[12] Toshniwal J, Chawlani R, Thawrani A, Sharma R, Arora A, Kotecha HL, et al. All ileo-cecal ulcers are not Crohn’s: Changing perspectives of symptomatic ileocecal ulcers. World Journal of Gastrointestinal Endoscopy. 2017; 9: 327–333. https://doi.org/10.4253/wjge.v9.i7.327.

[13] Goldstein NS. Isolated ileal erosions in patients with mildly altered bowel habits. A follow-up study of 28 patients. American Journal of Clinical Pathology. 2006; 125: 838–846. https://doi.org/10.1309/4PK0-G68M-2G1L-6X47.

[14] Fujimori S. Asymptomatic small intestinal ulcerative lesions: Obesity and Helicobacter pylori are likely to be risk factors. World Journal of Gastroenterology. 2021; 27: 4484–4492. https://doi.org/10.3748/wjg.v27.i28.4484.

[15] Chen H, Gao C, Li H, Li C, Wang C, Bai Z, et al. Factors of easy and difficult cecal intubation during unsedated colonoscopy. Revista Espanola De Enfermedades Digestivas. 2023; 115: 546–552. https://doi.org/10.17235/reed.2023.9283/2022.

[16] Zhang X, Yue Y, Liu S, Cong X, Wang W, Li J. Relationship between BMI and risk of impaired glucose tolerance and impaired fasting glucose in Chinese adults: a prospective study. BMC Public Health. 2023; 23: 14. https://doi.org/10.1186/s12889-022-14912-0.

[17] Inflammatory Bowel Disease Group, Chinese Society of Gastroenterology, Chinese Medical Association. Chinese consensus on diagnosis and treatment in inflammatory bowel disease (2018, Beijing). Journal of Digestive Diseases. 2021; 22: 298–317. https://doi.org/10.1111/1751-2980.12994.

[18] Kim SJ. Terminal ileum in screening colonoscopy: routine practice or risk-stratified approach? Clinical Endoscopy. 2025; 58: 696–697. https://doi.org/10.5946/ce.2025.213.

[19] Nardo GD, Esposito G, Ziparo C, Micheli F, Masoni L, Villa MP, et al. Enteroscopy in children and adults with inflammatory bowel disease. World Journal of Gastroenterology. 2020; 26: 5944–5958. https://doi.org/10.3748/wjg.v26.i39.5944.

[20] Kahveci AS, Mubarak MF, Perveze I, Daglilar ES. Differential to Terminal Ileitis: Terminal Ileum Neuroendocrine Tumor Identified on Screening Colonoscopy. Ochsner Journal. 2023; 23: 67–71. https://doi.org/10.31486/toj.22.0035.

[21] Nikolakis D, de Voogd FAE, Pruijt MJ, Grootjans J, van de Sande MG, D’Haens GR. The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease. International Journal of Molecular Sciences. 2022; 23: 1854. https://doi.org/10.3390/ijms23031854.

[22] Zhang H, Wang X, Zhang J, He Y, Yang X, Nie Y, et al. Crosstalk between gut microbiota and gut resident macrophages in inflammatory bowel disease. Journal of Translational Internal Medicine. 2023; 11: 382–392. https://doi.org/10.2478/jtim-2023-0123.

[23] Wan Y, Yuan J, Li J, Li H, Yin K, Wang F, et al. Overweight and underweight status are linked to specific gut microbiota and intestinal tricarboxylic acid cycle intermediates. Clinical Nutrition. 2020; 39: 3189–3198. https://doi.org/10.1016/j.clnu.2020.02.014.

[24] Pinart M, Dötsch A, Schlicht K, Laudes M, Bouwman J, Forslund SK, et al. Gut Microbiome Composition in Obese and Non-Obese Persons: A Systematic Review and Meta-Analysis. Nutrients. 2021; 14: 12. https://doi.org/10.3390/nu14010012.

[25] Patloka O, Komprda T, Franke G. Review of the Relationships Between Human Gut Microbiome, Diet, and Obesity. Nutrients. 2024; 16: 3996. https://doi.org/10.3390/nu16233996.

[26] Malesza IJ, Malesza M, Walkowiak J, Mussin N, Walkowiak D, Aringazina R, et al. High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review. Cells. 2021; 10: 3164. https://doi.org/10.3390/cells10113164.

[27] Sasidharan Pillai S, Gagnon CA, Foster C, Ashraf AP. Exploring the Gut Microbiota: Key Insights Into Its Role in Obesity, Metabolic Syndrome, and Type 2 Diabetes. The Journal of Clinical Endocrinology and Metabolism. 2024; 109: 2709–2719. https://doi.org/10.1210/clinem/dgae499.

[28] Fan S, Chen S, Lin L. Research progress of gut microbiota and obesity caused by high-fat diet. Frontiers in Cellular and Infection Microbiology. 2023; 13: 1139800. https://doi.org/10.3389/fcimb.2023.1139800.

[29] Busch CBE, Bergman JJGHM, Nieuwdorp M, van Baar ACG. Role of the Intestine and Its Gut Microbiota in Metabolic Syndrome and Obesity. The American Journal of Gastroenterology. 2024; 119: 1038–1046. https://doi.org/10.14309/ajg.0000000000002730.

[30] Neilson LJ, Bevan R, Panter S, Thomas-Gibson S, Rees CJ. Terminal ileal intubation and biopsy in routine colonoscopy practice. Expert Review of Gastroenterology & Hepatology. 2015; 9: 567–574. https://doi.org/10.1586/17474124.2015.1001744.

[31] Leiman DA, Jawitz NG, Lin L, Wood RK, Gellad ZF. Terminal ileum intubation is not associated with colonoscopy quality measures. Journal of Gastroenterology and Hepatology. 2020; 35: 1503–1508. https://doi.org/10.1111/jgh.14997.

[32] Li J, Ling F, Guo D, Zhao J, Cheng L, Chen Y, et al. The efficacy of mesalazine on nonspecific terminal ileal ulcers: A randomized controlled trial. Frontiers in Pharmacology. 2022; 13: 989654. https://doi.org/10.3389/fphar.2022.989654.

[33] Kumar R, Nath P, Anand AC, Misra P, Devisetty VJ, Tiwari A, et al. Combination of antimicrobials for non-specific isolated terminal ileal abnormalities - A randomized clinical trial. Indian Journal of Gastroenterology. 2023; 42: 658–667. https://doi.org/10.1007/s12664-023-01398-w.

[34] Petrolla AA, Katz JA, Xin W. The clinical significance of focal enhanced gastritis in adults with isolated ileitis of the terminal ileum. Journal of Gastroenterology. 2008; 43: 524–530. https://doi.org/10.1007/s00535-008-2191-8.

[35] Courville EL, Siegel CA, Vay T, Wilcox AR, Suriawinata AA, Srivastava A. Isolated asymptomatic ileitis does not progress to overt Crohn disease on long-term follow-up despite features of chronicity in ileal biopsies. The American Journal of Surgical Pathology. 2009; 33: 1341–1347. https://doi.org/10.1097/PAS.0b013e3181ad25b6.

[36] Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, et al. Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet. 2016; 387: 156–167. https://doi.org/10.1016/S0140-6736(15)00465-1.

[37] Lim WC, Hanauer S. Aminosalicylates for induction of remission or response in Crohn’s disease. The Cochrane Database of Systematic Reviews. 2010; Cd008870. https://doi.org/10.1002/14651858.CD008870.

[38] Gordon H, Minozzi S, Kopylov U, Verstockt B, Chaparro M, Buskens C, et al. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment. Journal of Crohn’s & Colitis. 2024; 18: 1531–1555. https://doi.org/10.1093/ecco-jcc/jjae091.

[39] He W, Li Q, Yang M, Jiao J, Ma X, Zhou Y, et al. Lower BMI cutoffs to define overweight and obesity in China. Obesity. 2015; 23: 684–691. https://doi.org/10.1002/oby.20995.

[40] Ding J, Chen X, Shi Z, Bai K, Shi S. Association of Metabolically Healthy Obesity and Risk of Cardiovascular Disease Among Adults in China: A Retrospective Cohort Study. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2023; 16: 151–159. https://doi.org/10.2147/DMSO.S397243.

[41] Mu L, Liu J, Zhou G, Wu C, Chen B, Lu Y, et al. Obesity Prevalence and Risks Among Chinese Adults: Findings From the China PEACE Million Persons Project, 2014–2018. Circulation: Cardiovascular Quality and Outcomes. 2021; 14: e007292. https://doi.org/10.1161/CIRCOUTCOMES.120.007292.

Funding

Independent Research Funding of General Hospital of Northern Theater Command(ZZKY2024018)